The Treasure Seekers

The Treasure Seekers

Jinghui Zhang, PhD, of Computational Biology, and David Ellison, MD, PhD, Pathology chair, recently discovered tiny changes that can transform a normal brain cell into a cancerous cell.

St. Jude scientists unearth genes driving the most common childhood tumor of the brain and spinal cord.

A café sits at the heart of St. Jude Children’s Research Hospital. Every day, its tables and candy-colored chairs host familiar scenes: a parent hugging a tired child, a nurse sipping a needed cup of coffee. But one day this spring, café patrons witnessed a more unusual spectacle—exultant scientists, laughing and celebrating.

“We were jumping up and down,” recalls Jinghui Zhang, PhD, of Computational Biology. Her collaborator, David Ellison, MD, PhD, Pathology chair, had just revealed a key piece of data. It clinched what the researchers already suspected: They had struck genetic gold.

2-year-old Juliauna Blackledge

The Pediatric Cancer Genome Project is yielding discoveries that may one day help patients with low-grade gliomas¬—children such as 2-year-old Juliauna Blackledge.

What they had discovered was a tiny change in the DNA of the cells in low-grade glioma, the most common childhood tumor of the brain and spinal cord. The alteration was so small they had almost missed it. Yet, as Ellison’s data proved, this tiny change was enough to turn a normal brain cell into something deadly.

As part of the St. Jude Children’s Research Hospital—Washington University Pediatric Cancer Genome Project, Zhang, Ellison and their colleagues used heavy-duty technology and know-how to scrutinize every bit of DNA in the tumor genomes of dozens of low-grade glioma patients.

The intense effort yielded significant rewards. When the dust settled, the researchers had discovered a slew of previously unknown genetic abnormalities driving low-grade gliomas. The genetic basis for more than 90 percent of these tumors is now understood.

Low grade glioma

“I’m very proud of what we accomplished,” Zhang says. “We work long hours, but it’s like hunting treasures to try to find these things.”

A major win was the discovery of two small changes responsible for more than half of hard-to-treat diffuse low-grade glioma cases. One of these mutations was so tricky to detect, the proof of its ability to cause cancer triggered the café-side victory celebration.

By discovering the genetic changes causing low-grade gliomas, Ellison hopes one day to help children with these tumors through new, targeted therapies. In fact, the recent findings suggest that many childhood low-grade gliomas may prove sensitive to drugs already in the pipeline.

“The pharmaceutical companies likely don’t have pediatric low-grade glioma in mind when they’re developing these drugs for much more common adult cancers,” Ellison says. “But we benefit from all that development work, because if we can show the relevance of new drugs to a kid’s disease, it gives us a new angle on how to treat the child.”

Abridged from Promise, Autumn 2013

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